A possible role for catecholamine neurotransmitters in the anticonvulsant activity of chlordiazepoxide

The role of catecholamines, in the central nervous system, as mediators of the anticonvulsant activity of chlordiazepoxide, was investigated. Chlordiazepoxide in doses of 2.5 mg/kg and 5.0 mg/kg provided dose-dependent protection from pentylenetetrazol-induced seizures in male albino mice. Treatment of mice with either α-methyl-p-tyrosine, phenoxybenzamine, propranolol or L-dopa, prior to the administration of chlordiazepoxide potentiated the anticonvulsant activity of chlordiazepoxide. This was reflected by an increase in the degree of protection from convulsions, a decrease in ED₅₀ value, and an increased time to onset of seizures in pretreated mice. Administration of disulfiram prior to the administration of chlordiazepoxide was shown to provide no significant increase in the anticonvulsant activity of chlordiazepoxide. These results have provided evidence for the role of catecholamine neurotransmitters as possible mediators of the anticonvulsant activity of chlordiazepoxide.